Study to Evaluate the Safety, Tolerability, and Efficacy of PEP-TISSEEL in Subjects With Chronic Radiation Ulcer

Rion LLC

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Chronic Radiation Ulcer

Treatments: Combination Product: PEP-TISSEEL; Drug: TISSEEL Fibrin Sealant KIT

Study type: Interventional

Funder types: Other; Industry; Other U.S. Federal agency

Identifiers

NCT06793748

PRO-00180

Details and patient eligibility

About

The goal of this clinical trial is to learn if drug Purified Exosome Product (PEP™) and Fibrin Sealant (TISSEEL® VH SD Kit) (PEP-TISSEEL) works to treat chronic radiation ulcer in adults and compare it with comparator TISSEEL. It will also learn about the safety of drug PEP-TISSEEL.

Enrollment: 184 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Participants in both study parts are eligible to be included if all of the following criteria apply:

Age and Sex

1. Males and females aged ≥ 18 years at the time of signing the informed consent. Informed Consent

2. Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

   Type of Participant and Disease Characteristics

3. Status post-radiation treatment, with radiation-induced ulcer. This includes participants with moist desquamation as well as full epidermal necrosis and superficial dermal ulcerations (this wound would otherwise be allowed to heal by secondary intention).

4. Index ulcer classified as Grade 1 to Grade 3 according to the NCI-CTCAE, Version 5.0

5. Area of index ulcer must be between 1 and 15 cm2 at screening and at randomization/baseline.

6. Have failed conservative treatments including attempts at washing and local wound care, and be seeking therapy

7. The chronic radiation ulcers are limited to cutaneous (skin) ulcers and not impacting mucosal (oral, nose, etc.) tissue. Sex and Contraceptive/Barrier Requirements

8. Must meet one of the following criteria:

   a. Female participants of non-childbearing potential defined as : i. Postmenopausal for at least 1 year (participant verbal confirmation acceptable), or surgically sterilized (i.e., hysterectomy or bilateral oophorectomy more than 3 months prior to screening); or ii. Bilateral tubal ligation more than 6 months prior to screening; or iii. Must have a negative β-hCG blood pregnancy test at screening and not be breastfeeding prior to being administered with the IP b. Male participants of non-childbearing potential are defined as those vasectomized participants whose vasectomy was performed 6 months prior to screening or those diagnosed as sterile by a physician c. Females and males of childbearing potential who practice an acceptable method of contraception defined as the use of any form of hormonal contraceptive, a barrier method with spermicide, condoms, intrauterine device, or abstinence from sexual intercourse starting at least 60 days prior to screening and continuing at least 30 days following the last treatment. Female will undergo pregnancy tests and must have a negative β-hCG blood pregnancy test at screening visit and negative urine pregnancy test at baseline visit and must not be breastfeeding prior to being administered with the IP. Other Inclusion Criteria

9. Participants must be deemed by Radiation Oncologist at or greater than 6 months status/post-treatment to be without evidence of local recurrence

10. Ability to comply with the study protocol

11. Participants must be willing to undergo all clinical investigation-related procedures and attend all required visits including all follow-up visits Exclusion Criteria

Participants in both study parts are excluded if any of the following criteria apply:

Medical Conditions

1. Study wound exhibits clinical signs and symptoms of infection at the screening visit
2. Any participant that has vascular compromise that is untreated as defined by as by defined abnormal invasive or non-invasive vascular studies
3. The index ulcer is within 2 cm of any other ulcer
4. The non-Cutaneous CRUs and ulcers impacting mucosal (oral, nose, etc.) tissue Liver Safety
5. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN) Prior/Concurrent Clinical Study Experience
6. Use of investigational drugs or biologics within 28 days prior to screening
7. Participation in another interventional clinical study in the past 30 days or concurrent participation in another interventional clinical study Diagnostic Assessments
8. Hemoglobin A1c (HbA1c) > 8%
9. Serum creatinine l > 2.5 mg/dL
10. Absolute neutrophil count of <500 neutrophils per mm3 over the course of enrollment
11. Positive test for HBV, HCV, HIV Other Exclusion Criteria
12. Active tanning, including the use of tanning booths, during the course of the study
13. Any participant who would be unable to safely monitor the infection status of the index ulcer at home and return for scheduled visits
14. Any participant with a life expectancy ≤ 6 months
15. Pregnancy, including a positive pregnancy test at screening, or lactation
16. Likely inability to comply with the protocol or cooperate fully with the Investigator and study site personnel
17. Known or suspected active abuse of alcohol, or non-prescription drugs
18. Participants who are incarcerated for any reason

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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184 participants in 4 patient groups, including a placebo group

Part 1-PEP-TISSEEL

Experimental group

Description:

Part 1(Phase1): Participants in the PEP-TISSEEL group will receive 1 topical application per week of 2 vials of PEP + 10 mL TISSEEL for 20 weeks (5 months).

Treatment:

Combination Product: PEP-TISSEEL

Combination Product: PEP-TISSEEL

Part 1(Phase1) -TISSEEL-Only

Placebo Comparator group

Description:

Part 1:Participants in the TISSEEL-Only group will receive 1 topical application per week of 10 mL TISSEEL for 20 weeks (5 months).

Treatment:

Drug: TISSEEL Fibrin Sealant KIT

Drug: TISSEEL Fibrin Sealant KIT

Part 2 (Phase2)-PEP-TISSEEL

Experimental group

Description:

Part 2: Participants in the PEP-TISSEEL group will receive 1 topical application per week of 2 vials of PEP + 10 mL TISSEEL for 20 weeks (5 months).

Treatment:

Combination Product: PEP-TISSEEL

Combination Product: PEP-TISSEEL

Part 2(Phase2)-TISSEEL-Only

Placebo Comparator group

Description:

Part 2:Participants in the TISSEEL-Only group will receive 1 topical application per week of 10 mL TISSEEL for 20 weeks (5 months).

Treatment:

Drug: TISSEEL Fibrin Sealant KIT

Drug: TISSEEL Fibrin Sealant KIT